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Peptides that mimic glycosaminoglycans: high-affinity ligands for a hyaluronan binding domain.

Identifieur interne : 002402 ( PubMed/Checkpoint ); précédent : 002401; suivant : 002403

Peptides that mimic glycosaminoglycans: high-affinity ligands for a hyaluronan binding domain.

Auteurs : M R Ziebell [États-Unis] ; Z G Zhao ; B. Luo ; Y. Luo ; E A Turley ; G D Prestwich

Source :

RBID : pubmed:11731299

Descripteurs français

English descriptors

Abstract

Hyaluronan (HA) is a non-sulfated glycosaminoglycan (GAG) that promotes motility, adhesion, and proliferation in mammalian cells, as mediated by cell-surface HA receptors. We sought to identify non-carbohydrate ligands that would bind to and activate cell-surface HA receptors. Such analogs could have important therapeutic uses in the treatment of cancer, wound healing, and arthritis, since such ligands would be resistant to degradation by hyaluronidase (HAse).

DOI: 10.1016/s1074-5521(01)00078-3
PubMed: 11731299


Affiliations:


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pubmed:11731299

Le document en format XML

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<nlm:affiliation>Department of Physiology and Biophysics, The University at Stony Brook, NY 11794-8661, USA.</nlm:affiliation>
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<wicri:regionArea>Department of Physiology and Biophysics, The University at Stony Brook, NY 11794-8661</wicri:regionArea>
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<name sortKey="Zhao, Z G" sort="Zhao, Z G" uniqKey="Zhao Z" first="Z G" last="Zhao">Z G Zhao</name>
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<name sortKey="Luo, Y" sort="Luo, Y" uniqKey="Luo Y" first="Y" last="Luo">Y. Luo</name>
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<name sortKey="Turley, E A" sort="Turley, E A" uniqKey="Turley E" first="E A" last="Turley">E A Turley</name>
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<name sortKey="Prestwich, G D" sort="Prestwich, G D" uniqKey="Prestwich G" first="G D" last="Prestwich">G D Prestwich</name>
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<keywords scheme="KwdEn" xml:lang="en">
<term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Binding Sites</term>
<term>Binding, Competitive</term>
<term>Extracellular Matrix Proteins (antagonists & inhibitors)</term>
<term>Extracellular Matrix Proteins (metabolism)</term>
<term>Glycosaminoglycans (antagonists & inhibitors)</term>
<term>Glycosaminoglycans (chemistry)</term>
<term>Humans</term>
<term>Hyaluronan Receptors (metabolism)</term>
<term>Hyaluronic Acid (antagonists & inhibitors)</term>
<term>Hyaluronic Acid (chemistry)</term>
<term>Ligands</term>
<term>Models, Molecular</term>
<term>Molecular Mimicry</term>
<term>Oligopeptides (chemistry)</term>
<term>Oligopeptides (metabolism)</term>
<term>Peptide Library</term>
<term>Protein Binding</term>
<term>Structure-Activity Relationship</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Acide hyaluronique ()</term>
<term>Acide hyaluronique (antagonistes et inhibiteurs)</term>
<term>Animaux</term>
<term>Banque de peptides</term>
<term>Fixation compétitive</term>
<term>Glycosaminoglycanes ()</term>
<term>Glycosaminoglycanes (antagonistes et inhibiteurs)</term>
<term>Humains</term>
<term>Liaison aux protéines</term>
<term>Ligands</term>
<term>Mimétisme moléculaire</term>
<term>Modèles moléculaires</term>
<term>Oligopeptides ()</term>
<term>Oligopeptides (métabolisme)</term>
<term>Protéines de la matrice extracellulaire (antagonistes et inhibiteurs)</term>
<term>Protéines de la matrice extracellulaire (métabolisme)</term>
<term>Relation structure-activité</term>
<term>Sites de fixation</term>
<term>Séquence d'acides aminés</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en">
<term>Extracellular Matrix Proteins</term>
<term>Glycosaminoglycans</term>
<term>Hyaluronic Acid</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en">
<term>Glycosaminoglycans</term>
<term>Hyaluronic Acid</term>
<term>Oligopeptides</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Extracellular Matrix Proteins</term>
<term>Hyaluronan Receptors</term>
<term>Oligopeptides</term>
</keywords>
<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr">
<term>Acide hyaluronique</term>
<term>Glycosaminoglycanes</term>
<term>Protéines de la matrice extracellulaire</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Oligopeptides</term>
<term>Protéines de la matrice extracellulaire</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Binding Sites</term>
<term>Binding, Competitive</term>
<term>Humans</term>
<term>Ligands</term>
<term>Models, Molecular</term>
<term>Molecular Mimicry</term>
<term>Peptide Library</term>
<term>Protein Binding</term>
<term>Structure-Activity Relationship</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Acide hyaluronique</term>
<term>Animaux</term>
<term>Banque de peptides</term>
<term>Fixation compétitive</term>
<term>Glycosaminoglycanes</term>
<term>Humains</term>
<term>Liaison aux protéines</term>
<term>Ligands</term>
<term>Mimétisme moléculaire</term>
<term>Modèles moléculaires</term>
<term>Oligopeptides</term>
<term>Relation structure-activité</term>
<term>Sites de fixation</term>
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<front>
<div type="abstract" xml:lang="en">Hyaluronan (HA) is a non-sulfated glycosaminoglycan (GAG) that promotes motility, adhesion, and proliferation in mammalian cells, as mediated by cell-surface HA receptors. We sought to identify non-carbohydrate ligands that would bind to and activate cell-surface HA receptors. Such analogs could have important therapeutic uses in the treatment of cancer, wound healing, and arthritis, since such ligands would be resistant to degradation by hyaluronidase (HAse).</div>
</front>
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<MedlineCitation Status="MEDLINE" Owner="NLM">
<PMID Version="1">11731299</PMID>
<DateCompleted>
<Year>2003</Year>
<Month>04</Month>
<Day>16</Day>
</DateCompleted>
<DateRevised>
<Year>2019</Year>
<Month>10</Month>
<Day>25</Day>
</DateRevised>
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<Journal>
<ISSN IssnType="Print">1074-5521</ISSN>
<JournalIssue CitedMedium="Print">
<Volume>8</Volume>
<Issue>11</Issue>
<PubDate>
<Year>2001</Year>
<Month>Nov</Month>
</PubDate>
</JournalIssue>
<Title>Chemistry & biology</Title>
<ISOAbbreviation>Chem. Biol.</ISOAbbreviation>
</Journal>
<ArticleTitle>Peptides that mimic glycosaminoglycans: high-affinity ligands for a hyaluronan binding domain.</ArticleTitle>
<Pagination>
<MedlinePgn>1081-94</MedlinePgn>
</Pagination>
<Abstract>
<AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Hyaluronan (HA) is a non-sulfated glycosaminoglycan (GAG) that promotes motility, adhesion, and proliferation in mammalian cells, as mediated by cell-surface HA receptors. We sought to identify non-carbohydrate ligands that would bind to and activate cell-surface HA receptors. Such analogs could have important therapeutic uses in the treatment of cancer, wound healing, and arthritis, since such ligands would be resistant to degradation by hyaluronidase (HAse).</AbstractText>
<AbstractText Label="RESULTS" NlmCategory="RESULTS">Peptide ligands that bind specifically to the recombinant HA binding domain (BD) of the receptor for hyaluronan-mediated motility (RHAMM) were obtained by screening two peptide libraries: (i) random 8-mers and (ii) biased 8-mers with alternating acidic side chains, i.e. XZXZXZXZ (X=all-L-amino acids except Cys, Lys, or Arg; Z=D-Asp, L-Asp, D-Glu, or L-Glu). Selectivity of the peptide ligands for the HABD was established by (i) detection of binding of biotin- or fluorescein-labeled peptides to immobilized proteins and (ii) fluorescence polarization of FITC-labeled peptides with the HABD in solution. HA competitively displaced binding of peptides to the HABD, while other GAGs were less effective competitors. The stereochemistry of four biased octapeptides was established by synthesis of the 16 stereoisomers of each peptide. Binding assays demonstrated a strong preference for alternating D and L configurations for the acidic residues, consistent with the calculated orientation of glucuronic acid moieties of HA.</AbstractText>
<AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Two classes of HAse-resistant peptide mimetics of HA were identified with high affinity, HA-compatible binding to the RHAMM HABD. This demonstrated that non-HA ligands specific to a given HA binding protein could be engineered, permitting receptor-specific targeting.</AbstractText>
</Abstract>
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